EP2521728B1 - Hydrate cristallin de darunavir et son procédé de préparation - Google Patents

Hydrate cristallin de darunavir et son procédé de préparation Download PDF

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Publication number
EP2521728B1
EP2521728B1 EP10765473.3A EP10765473A EP2521728B1 EP 2521728 B1 EP2521728 B1 EP 2521728B1 EP 10765473 A EP10765473 A EP 10765473A EP 2521728 B1 EP2521728 B1 EP 2521728B1
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EP
European Patent Office
Prior art keywords
darunavir
crystalline
water
darunavir hydrate
hydrate
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Not-in-force
Application number
EP10765473.3A
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German (de)
English (en)
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EP2521728A2 (fr
Inventor
Manjinder Singh Phull
Dharmaraj Ramachandra Rao
Rajendra Narayanrao Kankan
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Cipla Ltd
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Cipla Ltd
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Publication of EP2521728A2 publication Critical patent/EP2521728A2/fr
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Publication of EP2521728B1 publication Critical patent/EP2521728B1/fr
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
    • C07D493/04—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/21—Esters, e.g. nitroglycerine, selenocyanates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
    • A61K31/341—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the present invention relates to a stable polymorphic form of darunavir. More particularly, it relates to a hydrated form of darunavir and a process for preparation thereof.
  • US20050250845 discloses various pseudopolymorphs of darunavir and processes for their preparation. According to this application, "pseudopolymorph” is defined as a crystalline form of a compound in which solvent molecules are incorporated in the lattice structure.
  • the Form B disclosed in the patent application is a pseudopolymorph wherein water is used as solvent.
  • the thermogravimetric experiments of the Form B shows weight loss of 3.4% in the temperature range 25-78°C (water), 5.1% in the temperature range 25-110°C (ethanol and water) and further 1.1% weight loss (ethanol) in temperature range 110-200° C. Further at the drying step the Form B showed about 5.6% weight loss.
  • the obtained dried product was hygroscopic and it adsorbed up to 6.8% water at high relative humidity.
  • Amorphous form of darunavir is disclosed in US20050250845 and the publication in J.Org. Chem. 2004, 69, 7822 - 7829 .
  • the object of the present invention is to provide stable polymorph of darunavir, free from other pseudopolymorphs or solvates, and process for its preparation.
  • the present invention relates to a polymorphic form of darunavir. More particularly the invention relates to hydrated form of darunavir.
  • the darunavir hydrate of the present invention is a true hydrate.
  • the "true hydrate” hereinafter referred as 'Form C' is defined as a hydrate form which is crystalline, stable, non-hygroscopic in nature and does not contain any solvent molecule.
  • the present invention provides Form C characterised by powder X-ray diffraction spectrum as shown in Fig. 1 .
  • Form C is further characterized by thermogravimetric curve as shown in Fig. 2 .
  • the present invention further provides a process for preparation of Form C having water content in range of 7 to 8.5%, as determined by the Karl Fischer method. Also the present invention provides a pharmaceutical composition comprising Form C of darunavir with one or more pharmaceutically acceptable excipients.
  • the present invention provides a crystalline form of darunavir (Form C) which is essentially a true hydrate as defined above. It is a stable polymorphic form that does not undergo any polymorphic transition under various humid conditions.
  • Crystalline darunavir hydrate Form C of the present invention comprises 1 to 3 molecules of water, which corresponds to a water content ranging from about 7.0 to 8.5% and further the crystalline darunavir hydrate of the present invention is substantially free of any organic solvent
  • Form C of the present invention is essentially free of any pseudopolymorphs or solvates disclosed in the prior art.
  • substantially free refers to darunavir Form C with residual solvent content as per ICH guidelines.
  • the darunavir Form C of the present invention has residual solvent content not more than 500 ppm.
  • the X-ray powder diffraction pattern of the hydrated form of present invention was measured on a Rigaku Dmax 2200 advanced X-ray powder diffractometer with a copper-K- ⁇ radiation source.
  • Darunavir hydrate Form C of the present invention has X-ray powder diffractogram pattern with peaks at 2 ⁇ values as listed in Table 1.
  • Table 1 XRD values of Darunavir Form C Diffraction angles ( ⁇ 0.2 2 ⁇ °) Relative Intensity 7.12 100 9.42 34 10.04 13 10.34 16 11.36 30 12.94 20 13.86 76 16.78 90 17.54 75 18.38 23 18.56 14 18.90 50 19.14 79 20.14 23 20.64 46 20.88 60 21.28 97 21.74 21 21.92 14 22.84 65 23.20 41 23.50 29 23.68 30 25.20 12 26.44 15 27.54 15 28.34 42 29.28 12 30.44 18 32.80 12
  • the present invention further provides a process for the preparation of Form C wherein 1-methylpyrrolidine-2,5-dione(3R,3aS,6aR)-tetrahydro-2H-furo[2,3-b]furan-3-yl carbonate is reacted with 4-amino-N-(3-amino-2-hydroxy-4-phenylbutyl)-N-isobutylbenzenesulfonamide to obtain a residue which is stirred in a mixture of water miscible solvent and water to obtain a solid which is dried to obtain darunavir hydrate Form C.
  • the present invention also provides a process of converting the pseudopolymorphs or solvates of darunavir to a stable polymorph Form C wherein the pseudopolymorph or solvate is stirred in a mixture of water miscible solvent and water and then filtered. The resulting solid is further stirred in water, filtered and dried to obtain Form C.
  • the water miscible solvent used in the process of present invention may be selected from methanol, ethanol, propanol, isopropanol, acetone, etc., but preferably the solvent used is methanol.
  • the solid product obtained on filtration is preferably dried under vacuum.
  • the solid product is preferably dried at a temperature of not more than 40°C.
  • the darunavir Form C of the present invention has a water content between 7.0 to 8.5%, as determined by the Karl Fischer method.
  • thermogravimetric analysis indicating the change in mass as the sample is heated, cooled or held constant, of darunavir hydrate Form C of present invention showed about 5.5 - 7.5% weight loss.
  • the thermogravimetric curve of darunavir Form C is depicted in Figure 2 .
  • Form C of the present invention on drying at elevated temperature is converted to stable, non-hygroscopic amorphous darunavir which forms another aspect of the present invention.
  • the amorphous darunavir obtained by the process of present invention is characterised by XRD pattern which is provided in Figure 3 .
  • the present invention also relates to a pharmaceutical composition
  • a pharmaceutical composition comprising crystalline darunavir Form C and a pharmaceutically acceptable carrier or diluent.
  • the present invention relates to a pharmaceutical composition
  • a pharmaceutical composition comprising amorphous darunavir prepared by the process of present invention and a pharmaceutically acceptable carrier or diluent.
  • reaction contents were quenched with saturated sodium bicarbonate (116 ml) and stirred.
  • the organic layer was washed with water (50 ⁇ 2 ml) and concentrated under reduced pressure.
  • isopropanol was added and contents heated to reflux.
  • the reaction was cooled to 25-30°C and filtered.
  • reaction mass was heated to 65 ⁇ 2°C.
  • the reaction mass was chilled, filtered and then washed with toluene to obtain 33.6 g of darunavir.
  • Darunavir Form C obtained from any of the examples 2 to 4, when dried under vacuum at 60 ⁇ 2°C for 8 hours yielded stable and non-hygroscopic amorphous darunavir, having an XRD pattern as shown in Fig 3 .
  • Darunavir Hydrate From C was subjected to hygroscopicity study and the test was performed as per the method given in British Pharmacopoeia. 57.6456 g of darunavir hydrate Form C was exposed at 25°C and 85% RH (relative humidity) for 24 hours and the weight of the sample was recorded as 57.6459 g. A weight change of 0.0003 g was observed which correspond to 0.06% weight change. As per the test a sample is of non-hygroscopic nature if the weight change observed is less than 0.2%. From the results it can be concluded that darunavir hydrate Form C is a non-hygroscopic material, suitable for pharmaceutical preparation.
  • Darunavir hydrate Form C was subjected to long term storage stability (6 months) under normal condition i.e 30 ⁇ 2°C and 65 ⁇ 5% RH (relative humidity) and under accelerated conditions i.e 40 ⁇ 2°C and 75 ⁇ 5 % RH (relative humidity) and it was found that there was no significant increase or decrease in the moisture content or HPLC purity of darunavir hydrate form C. Thus indicating that the Form C of the present invention is stable and suitable for pharmaceutical use.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Virology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • AIDS & HIV (AREA)
  • Communicable Diseases (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Oncology (AREA)
  • Emergency Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Medicinal Preparation (AREA)
  • Plural Heterocyclic Compounds (AREA)

Claims (9)

  1. Darunavir cristallin hydraté comprenant pas plus de 500 ppm d'un solvant non aqueux, caractérisé en ce que le darunavir cristallin hydraté a une teneur en eau dans la gamme de 7,0 à 8,5 % et est non hygroscopique.
  2. Darunavir cristallin hydraté selon la revendication 1, comprenant pas plus de 500 ppm de méthanol, de dichlorure de méthylène, d'acétate d'éthyle, de tétrahydrofurane, de triéthylamine, de toluène et d'éthanol.
  3. Darunavir cristallin hydraté selon la revendication 1, ayant un diagramme de DRX selon le tableau suivant, dans lequel la diffraction des rayons X est mesurée avec une source utilisant le rayonnement Kα du cuivre : Angles de diffraction (± 0,2 2θ°) Intensité relative 7,12 100 9,42 34 10,04 13 10,34 16 11,36 30 12,94 20 13,86 76 16,78 90 17,54 75 18,38 23 18,56 14 18,90 50 19,14 79 20,14 23 20,64 46 20,88 60 21,28 97 21,74 21 21,92 14 22,84 65 23,20 41 23,50 29 23,68 30 25,20 12 26,44 15 27,54 15 28,34 42 29,28 12 30,44 18 32,80 12
  4. Composition pharmaceutique comprenant du darunavir cristallin hydraté selon l'une quelconque des revendications 1 à 3, éventuellement en combinaison avec un ou plusieurs excipients pharmaceutiquement acceptables.
  5. Darunavir cristallin hydraté selon l'une quelconque des revendications 1 à 3, pour une utilisation dans le traitement d'une infection par le VIH.
  6. Utilisation de darunavir cristallin hydraté selon l'une quelconque des revendications 1 à 3 dans la fabrication d'un médicament pour une utilisation dans le traitement d'une infection par le VIH.
  7. Procédé de préparation de darunavir hydraté comprenant l'agitation de darunavir, ayant au moins un solvant non aqueux dans sa structure cristalline, dans un mélange d'un solvant miscible à l'eau et d'eau; puis la filtration du mélange pour obtenir un solide; l'agitation du solide dans de l'eau; la filtration du mélange solide/eau et son séchage pour obtenir du darunavir cristallin hydraté selon l'une quelconque des revendications 1 à 3.
  8. Procédé de préparation de darunavir hydraté selon la revendication 7, dans lequel le solvant miscible à l'eau est le méthanol.
  9. Procédé de préparation de darunavir amorphe comprenant le séchage de darunavir cristallin hydraté préparé selon la revendication 7 ou 8, à haute température, pour obtenir du darunavir amorphe.
EP10765473.3A 2010-01-05 2010-10-06 Hydrate cristallin de darunavir et son procédé de préparation Not-in-force EP2521728B1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN33MU2010 2010-01-05
PCT/GB2010/001874 WO2011083287A2 (fr) 2010-01-05 2010-10-06 Polymorphe de darunavir et son procédé de préparation

Publications (2)

Publication Number Publication Date
EP2521728A2 EP2521728A2 (fr) 2012-11-14
EP2521728B1 true EP2521728B1 (fr) 2016-09-07

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EP10765473.3A Not-in-force EP2521728B1 (fr) 2010-01-05 2010-10-06 Hydrate cristallin de darunavir et son procédé de préparation

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US (2) US20130029945A1 (fr)
EP (1) EP2521728B1 (fr)
JP (2) JP2013516397A (fr)
KR (1) KR20120123077A (fr)
AU (1) AU2010340799B2 (fr)
CA (1) CA2785998A1 (fr)
NZ (1) NZ600994A (fr)
WO (1) WO2011083287A2 (fr)
ZA (1) ZA201204365B (fr)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7700645B2 (en) * 2002-05-16 2010-04-20 Tibotec Pharmaceuticals Ltd. Pseudopolymorphic forms of a HIV protease inhibitor
US8921415B2 (en) 2009-01-29 2014-12-30 Mapi Pharma Ltd. Polymorphs of darunavir
ES2516916T3 (es) 2010-01-28 2014-10-31 Mapi Pharma Limited Procedimiento para la preparación de darunavir e intermedios de darunavir
WO2013114382A1 (fr) 2011-12-05 2013-08-08 Mylan Laboratories Ltd Darunavir cristallin
CN103509031B (zh) * 2012-06-20 2016-04-27 上海迪赛诺药业有限公司 制备达芦那韦无定形物的方法
ES2848216T3 (es) 2012-07-24 2021-08-05 Laurus Labs Ltd Un proceso para la preparación de Darunavir
WO2016092525A1 (fr) 2014-12-12 2016-06-16 Lupin Limited Darunavir n-propanol solvate et son procédé de préparation
CN106854212A (zh) * 2015-12-08 2017-06-16 浙江九洲药业股份有限公司 一种达芦那韦无定型的制备方法
CN106242307A (zh) * 2016-08-11 2016-12-21 京东方科技集团股份有限公司 用于强化制品的边缘的方法、玻璃及显示装置
WO2018081292A1 (fr) * 2016-10-27 2018-05-03 Gilead Sciences, Inc. Formes cristallines de base libre de darunavir, hydrate, solvates et sels de celui-ci
CN108727401A (zh) * 2017-04-20 2018-11-02 盐城迪赛诺制药有限公司 达鲁那韦新晶型及其制备方法和应用
CN108794498A (zh) * 2017-05-03 2018-11-13 江苏瑞科医药科技有限公司 一种达芦那韦无定型的制备方法
CN109053753A (zh) * 2018-08-05 2018-12-21 浙江大学 一种制备达卢那韦二水合物晶型的方法

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DK0715618T3 (da) 1993-08-24 1999-08-23 Searle & Co Hydroxyethylaminosulfonamider til anvendelse som inhibitorer af retrovirale proteaser
DK1088098T4 (en) 1998-06-23 2015-09-14 Us Of America Represented By The Secretary Dept Of Health And Human Services Fitnessassay and methods for reducing HIV resistance to therapy
US7700645B2 (en) * 2002-05-16 2010-04-20 Tibotec Pharmaceuticals Ltd. Pseudopolymorphic forms of a HIV protease inhibitor
DE602004021640D1 (de) 2003-12-23 2009-07-30 Tibotec Pharm Ltd Verfahren zur herstellung von (1s,2r)-3-ää(4-aminophenyl)sulfonylü(isobutyl)aminoü-1-benzyl-2-hydroxypropylcarbamidsäure-(3r,3as,6ar)-hexahydrofuroä2,3-büfuran-3-ylester
US8703980B2 (en) * 2009-09-17 2014-04-22 Siva Rama Prasad Vellanki Process for the preparation of darunavir
CN102686594A (zh) * 2009-12-16 2012-09-19 熙德隆研究基金会 地瑞那韦的多晶型物

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
ARUN K. GHOSH ET AL: "Design, Synthesis, Protein-Ligand X-ray Structure, and Biological Evaluation of a Series of Novel Macrocyclic Human Immunodeficiency Virus-1 Protease Inhibitors to Combat Drug Resistance", JOURNAL OF MEDICINAL CHEMISTRY, vol. 52, no. 23, 10 December 2009 (2009-12-10), pages 7689 - 7705, XP055110676, ISSN: 0022-2623, DOI: 10.1021/jm900695w *
SURLERAUX D L N G ET AL: "Discovery and Selection of TMC114, a Next Generation HIV-1 Protease Inhibitor", JOURNAL OF MEDICINAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY, US, vol. 48, no. 6, 24 March 2005 (2005-03-24), pages 1813 - 1822, XP008122471, ISSN: 0022-2623, [retrieved on 20041005], DOI: 10.1021/JM049560P *
VAN GYSEGHEM E ET AL: "Solid state characterization of the anti-HIV drug TMC114: Interconversion of amorphous TMC114, TMC114 ethanolate and hydrate", EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES, ELSEVIER, AMSTERDAM, NL, vol. 38, no. 5, 8 December 2009 (2009-12-08), pages 489 - 497, XP026764329, ISSN: 0928-0987, [retrieved on 20090924], DOI: 10.1016/J.EJPS.2009.09.013 *

Also Published As

Publication number Publication date
JP2016028085A (ja) 2016-02-25
CA2785998A1 (fr) 2011-07-14
AU2010340799B2 (en) 2015-06-11
NZ600994A (en) 2014-04-30
JP2013516397A (ja) 2013-05-13
WO2011083287A2 (fr) 2011-07-14
ZA201204365B (en) 2013-12-23
EP2521728A2 (fr) 2012-11-14
KR20120123077A (ko) 2012-11-07
US20130029945A1 (en) 2013-01-31
AU2010340799A1 (en) 2012-07-05
US20150141383A1 (en) 2015-05-21
WO2011083287A3 (fr) 2011-09-15

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